Columbia University Study Reveals New Causes of Common Lymphoma
NEW YORK — Cancer researchers at Columbia University in New York have found a multitude of new genetic mutations that cause a common type of lymphoma.
“Our findings not only show that these mutations can contribute to diffuse large B cell lymphoma, but they identify an approach that should be useful for the analysis of other types of tumors,” said Dr. Riccardo Dalla-Favera, director of the Institute for Cancer Genetics at Columbia University Vagelos College of Physicians and Surgeons, who led the study.
The research team’s full findings were published in the journal Nature.
Diffuse large B cell lymphoma is the most common type of human hematologic malignancy and is fast-growing and aggressive.
Although treatment can now cure about two thirds of patients, the remaining patients have poor outcomes and new treatment strategies are needed, the university said in a press release.
Until now, what researchers knew about DLBCL was based on lymphoma-causing mutations found in the genome’s protein-coding genes. It was a logical place to begin, since these genes contain the instructions (or code) for making proteins, which carry out most of a cell’s functions.
But 98% of the human genome does not contain code for making proteins. Previously mischaracterized as “junk,” non-coding DNA is now known to have many functions, including critical roles in the regulation of gene expression.
In the new study, the Columbia researchers found that certain areas of the non-coding genome — called super-enhancers — are mutated in more than 90% of DLBCL tumors and may be necessary to sustain the cancer. Super-enhancers control the expression of one or more genes in the same chromosome.
The researchers found that the genetic correction of specific recurrent mutations within these distinct super-enhancers restored the regulation of the cancer-causing genes and led to tumor death, indicating that the tumor was dependent on the mutated super-enhancers.
The findings also reveal a new level of genetic complexity behind DLBCL that could help explain why this cancer has many different subtypes with diverse behaviors, the research hospital said.
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